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临床试验/NCT00479960
NCT00479960Unknown早期 1 期

Effect of Dietary Supplementation With Omega-3 Fatty Acids on Human Sperm Characteristics, a Preliminary Study

Hadassah Medical Organization1 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2007年6月最近更新:
适应症

试验速览

阶段
早期 1 期
入组人数
20
试验地点
1
主要终点
sperm count

研究概览

简要总结

The phospholipids of mammalian spermatozoa possess a distinctive fatty acid composition with high proportion of long chain polyunsaturated fatty acids. The lipid composition is a major determinant of the membrane flexibility and sperm motility required for proper fertilization. It also influences the sperm plasma membrane's fluidity, chilling sensitivity and thermotropic lipid phase transition (LPT) and these parameters determine our ability to cryopreserve these cells. Our hypotheses is that by providing dietary supplementation of omega-3 polyunsaturated fatty acids an improvement of sperm parameters (number, motility, viability) can be achieved. We also expect alteration spermatozoal plasma membrane fatty acid composition, making it more chilling resistant.

Experimental methodology: 1) Characterize fatty acid composition of the spermatozoa of normal and abnormal spermatozoa by gas chromatography. 2) Characterize sperm plasma membrane LPT by FTIR spectrometer. 3) Run a randomized double-blind, placebo controlled, crossed-over dietary fatty acid supplementation pilot trial in human sub-fertile patients. Large scale trial will follow, if justified. In both trials sperm characterization of each participant will be conducted before, during and following the trial.

Subfertile males will benefit greatly if their sperm parameters can be improved and cryopreserved while ensuring enhanced post-thawing survival. We believe that changing the fatty acid composition of sperm plasma membrane by simple dietary means will open the way to improve the fertility of those that needs it the most.

详细描述

The phospholipids of mammalian spermatozoa possess a distinctive and highly unusual fatty acid composition, the most unique feature of which is a very high proportion of long chain (C20-22) highly polyunsaturated fatty acyl groups. In most mammals, docosahexaenoic acid (DHA; 22:6,n-3) is the dominant polyunsaturated fatty acid (PUFA) although, in several species, docosapentaenoic acid (22:5,n-6) is also a major component 2. The lipid composition is a major determinant of the membrane flexibility required for the characteristic flagella movement of spermatozoa and for the fusogenic properties of the membranes associated with the acrosome reaction and fertilization. In addition, it has been demonstrated that lipid-derived mediators are involved in various signal transduction mechanisms that regulate spermatozoa functions.

Sperm motility was therefore closely correlated with fertility, yet factors controlling sperm motility in humans are not fully understood 12. The amount of PUFA, mainly DHA, and to a lesser extent eicosapentaenoic acid (EPA), was showed to be positively associated with sperm motility and essential for optimal fertility. The reduction in the amount of DHA in sperm lipids have been correlated with reduced sperm concentration, sperm progressive motility and the proportion of cells with normal morphology. In asthenozoospermic (poor sperm forward motility), the levels of DHA (and total PUFA) was found to be lower than in normozoospermic individuals despite similar serum fatty acid composition 18. Broiler spermatozoa rich in EPA or DHA or both showed significantly increased fertility following artificial insemination (AI).

Chilling injury to mammalian gametes has been described as the irreversible damage that occurs upon cooling to low, but non-freezing, temperatures. Several studies suggested that chilling injury is the major limiting factor for successful gamete cryopreservation. Other studies suggested that membranes are the primary sites for structural and functional chilling injury in sperm and oocytes. Additionally, membrane chilling injury is dependent on the biochemical and biophysical properties of membranes. The plasma membrane thermotropic lipid phase transition (Tm) from the fluid liquid crystalline phase to the more rigid gel phase is associated with chilling injury. When membrane lipids undergo lipid phase transition (LPT), fluidity decreases and the structure and functioning of the membrane change. As a result, the membrane permeability increases and the cells are damaged. The temperature at which Tm occurs is greatly affected by the fatty acid composition of the membrane. Membranes consisted of lipids with multiple unsaturations or short carbon chains are more fluid at low temperatures. The ability of the spermatozoal plasma membrane to resist structural damage during cryopreservation may therefore be related to its fatty acids composition and the strength of the bonds between membrane components 38. It was shown, for example, that spermatozoa of Asian elephants, which are more chilling sensitive than African elephant sperm, contain lower concentration of PUFA in their membranes and are especially poor in DHA.

There are several ways to change the chilling sensitivity and Tm in mammalian gametes. Spermatozoa can spontaneously interact with liposomes as was described in several studies. Previous work suggested that phospholipids adsorbed on to the sperm cells, which were then cooled to 4oC, increased the chilling resistance of the sperm cells from bovine, ram and elephant.

The relationship between dietary components and reproduction is well established. Follicular maturation, ovulation and oestrus in the female, and libido and fertility in the male, might all be adversely affected by undernutrition. Men with infertile semen were found to consume less omega-3 fatty acids than fertile men, and a significant correlation was established between the consumption of alpha-linolenic acid (18:3n-3) on the one hand and sperm concentration and progressive motility on the other hand. In boar, the output of the accessory glands, but not the output of spermatozoa by the testes, was affected by the reduced feed intake and is likely to reflect a suppression of androgen secretion. Various reports showed that enrichment of diet with PUFA can alter the biophysical properties or reproductive performance of mammalian and avian sperm and oocytes.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Crossover
主要目的
Treatment
盲法
Double

入排标准

性别
Male
接受健康志愿者

入选标准

  • Patients with asthenozoospermia (low progressive motility), teratozoopermia (abnormal morphology) and/or oligozoospermia (low sperm count)

排除标准

  • 未提供

结局指标

主要结局

sperm count

时间窗: 10 weeks

次要结局

  • sperm Lipid phase transition determination(10 weeks)

研究者

申办方类型
Other

研究点 (1)

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